Impact of Prolonged Perioperative Sedation on Infant Brain

围手术期长期镇静对婴儿大脑的影响

• 批准号: 10645492
• 负责人: DUSICA BAJIC
• 金额: $ 28.26万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645492
• 关键词: 1 year old; Address; Age; Age Months; Amygdaloid structure; Anesthesia procedures; Anisotropy; Award; Basal Ganglia; Brain; Brain region; Characteristics; Chest; Child; Childhood; Clinical; Clinical Data; Collaborations; Complex; Congenital Abnormality; Corpus Callosum; Critical Care; Critical Illness; Data; Data Collection; Dependence; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Drug Modulation; Early identification; Esophageal Atresia; Evaluation; Exhibits; Exposure to; Extracorporeal Circulation; Foundations; Future; Gestational Age; Goals; Growth; Human; Incidence; Infant; Infant Care; Knowledge; Lead; Life; Liquid substance; Longitudinal cohort study; Magnetic Resonance Imaging; Manuscripts; Maps; Measures; Mission; National Institute of Child Health and Human Development; National Institute of Drug Abuse; Neonatal; Neurocognitive; Neurologic Effect; Neurotransmitters; Nociception; Operative Surgical Procedures; Opioid; Outcome; Outcome Study; Pain; Pathway interactions; Pediatric Radiologist; Perioperative; Perioperative Care; Pharmaceutical Preparations; Physical Dependence; Play; Postoperative Period; Premature Infant; Publications; Reporting; Research; Risk; Role; Scanning; Sedation procedure; Sensory; Shapes; Site; Socioeconomic Status; Specificity; Structure; Techniques; Thalamic structure; Time; Toddler; United States; age related; brain abnormalities; brain magnetic resonance imaging; brain size; brain volume; clinical care; cohort; disability; experience; gastrointestinal; gray matter; high risk infant; human old age (65+); improved; infancy; innovation; international center; medical complication; neonate; neurobehavioral; neurodevelopment; neuroimaging; neuroprotection; novel; opiate tolerance; opioid exposure; pain processing; postnatal; premature; prevent; prognostic indicator; prospective; recruit; repaired; sex; tool; tractography; white matter

ABSTRACT Prolonged sedation treatment is currently considered standard practice in the safe and compassionate care of critically ill neonates and infants despite leading to opioid tolerance and a high incidence (35-57%) of physical dependence. A unique cohort of infants with congenital long-gap esophageal atresia (EA) undergoes complex perioperative critical care necessitating extraordinarily prolonged sedation (on the scale of weeks). Although our group recently reported decreased brain size and delayed brain growth in term-born infants following long-gap EA repair with prolonged postoperative sedation, there is a fundamental gap in our knowledge of (i) underlying mechanisms and (ii) long-term neurodevelopmental outcomes. Guided by strong preliminary data, this proposal will address 3 key gaps in our knowledge: (1) timing of brain findings (pre vs. during perioperative repair); (2) regional specificity (gray vs. white matter) of (mal)adaptations; as well as (3) infant brain and clinical correlates to early neurodevelopmental outcomes at 1-year of age. The study will employ structural MRI techniques to address these aims. Selected term-born and premature infants with short-gap (brief pain/sedation treatment) and long-gap EA (prolonged sedation treatment) will be scanned twice (AIM 1): before (as neonates), and after complex perioperative critical care (at 4(±1) months of age). Early neurodevelopmental outcomes will be evaluated using standard approaches (AIM 2). The findings will inform (I) mechanisms of brain (mal)adaptations associated with delayed vs. abnormal brain development in infants exposed to prolonged sedation; (II) identify early diagnostic and prognostic indicators for longitudinal neurocognitive correlates; and (III) inform future development of neonatal/infant therapies to mitigate the neurological effects in vulnerable infants exposed to prolonged sedation. Our application aligns with the goals of the National Institute of Child Health and Human Development (NICHD) and National Institute of Drug Abuse (NIDA) to improve the lives of children throughout all stages of development. We established the feasibility serving critical data collection, and we assembled an interdisciplinary team of experts for its successful completion. This research is innovative in that it encompasses a selected group of term-born infants exposed to prolonged sedation associated with dependence to drugs of sedation; novel in that it will investigate underlying mechanisms and neurodevelopmental impact of complex thoracic non-cardiac critical care; and significant in that it is expected to evolve pediatric critical care by developing novel adjunct therapies for age-specific pain and sedation treatment in the United States and the world.

抽象的 延长的镇静处理目前被认为是在安全和富有同情心的护理中的标准实践 尽管导致阿片类药物耐受性和高事件（35-57％），但重病的新生儿和婴儿疾病和婴儿 依赖。与先天性长间隙食道闭锁（EA）的独特小组进行复合体 长时间镇静所需的围手术期重症监护（在数周的规模上）。虽然我们的 据报道，据报道，最近的小组减少了大脑大小和长期脑部出生婴儿的脑大小的延迟 EA维修长时间的术后镇静剂，我们对（i）基础存在根本差距 机制和（ii）长期神经发育结果。 在强大的初步数据的指导下，该建议将解决我们知识中的3个关键差距：（1）大脑的时机 调查结果（Pre vs.定期维修）； （2）（MAL）适应的区域特异性（灰色与白质）； 以及（3）婴儿的大脑和临床与1岁大的早期神经发育结局相关。这 研究将采用结构性MRI技术来解决这些目标。选定的期限出生和早产婴儿 将扫描短间隙（短暂疼痛/镇静处理）和长间隙EA（延长镇静处理） 两次（AIM 1）：（作为新生儿）和复杂的周期性重症监护（在4（±1）个月大）之后。早期的 神经发育结果将使用标准方法进行评估（AIM 2）。 这些发现将告知（i）大脑的机制（MAL）适应与延迟和大脑异常相关的机制 暴露于长时间镇静的婴儿的发展； （ii）确定早期诊断和预后指标 纵向神经认知相关； （iii）告知新生儿/婴儿疗法的未来发展以减轻 暴露于长时间镇静的脆弱婴儿中的神经系统作用。我们的应用程序与目标保持一致 国家儿童健康与人类发展研究所（NICHD）和国家药物滥用研究所 （NIDA）在整个发展的所有阶段都改善儿童的生活。我们确定了可行性 为关键数据收集服务，我们为其成功组成了一个跨学科的专家团队 完成。这项研究具有创新性，因为它涵盖了一组所选的年前出生婴儿 长时间与镇静药物有关的镇静；小说，它将调查基础 复杂的胸非心脏重症监护的机制和神经发育影响；和意义重大 预计将通过开发新颖的辅助疗法来发展小儿重症监护 美国和世界的镇静处理。